Protective and therapeutic effect of heparin in acute pancreatitis.
The initiation and progression of acute pancreatitis is associated with disturbances in pancreatic microcirculatory. Microcirculatory disorders contribute to multiorgan dysfunction syndrome in the course of acute pancreatitis. The aim of this study was to determine the influence of heparin administration on the development and the course of ischemia/reperfusion-induced pancreatitis.


METHODS
Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. In the first series of studies, heparin was administered 0.5 h before induction of acute pancreatitis and the severity of acute pancreatitis was assessed after 6-h reperfusion. In the second series of studies, heparin was administered twice a day, starting 24 h after the initiation of reperfusion. In both series of studies, heparin was administered subcutaneously at the dose of 150 U/kg.


RESULTS
Treatment with heparin, before induction of pancreatitis, inhibits the development of morphological signs of acute pancreatitis and reduced the pancreatitis-evoked increase in plasma level of pancreatic enzymes and pro-inflammatory interleukin-1beta. These effects have been accompanied with improvement of pancreatic blood flow, pancreatic DNA synthesis and reduction in plasma concentration of D-dimer. Administration of heparin after induction of acute pancreatitis accelerates normalization of pancreatic histology, and reduces biochemical markers of the severity of acute pancreatitis. These effects have been accompanied with the improvement of pancreatic circulation, increase in APTT and reduction in plasma D-dimer level.


CONCLUSIONS
Treatment with heparin inhibits the development of ischemia/reperfusion-induced pancreatitis and accelerates pancreatic regeneration in the course of this disease.
Ceranowicz
P
P
Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
Dembinski
A
A
Warzecha
Z
Z
Dembinski
M
M
Cieszkowski
J
J
Rembisz
K
K
Konturek
S J
SJ
Kusnierz-Cabala
B
B
Tomaszewska
R
R
Pawlik
W W
WW
D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology
D000925:Anticoagulants; D006493:Heparin